PubMed Health⌕ Search

Biomedical subjects

D M Vázquez

Publications and source records attributed to D M Vázquez.

16 recordsLinked to original sources
PubMed2000

Maternal deprivation regulates serotonin 1A and 2A receptors in the infant rat.

UNLABELLED: Several studies have demonstrated that 5-HT1A and 5-HT2A receptors are altered in rat brain following chronic stress. While this is true in the adult animal, this may be different in the developing animal, which has a limited corticosterone response to acute challenges between days 3 and 14 of life. METHODS: We investigated the effect of maternal deprivation on 5-HT2A and 5-HT1A receptor mRNA levels in the developing brain. In situ hybridization was used to quantify gene expression in rat pups at three ages: 6, 9, and 12 days old. In each age group, half were maternally deprived for 24 h and half were kept with their mothers. Maternally deprived animals showed elevated ACTH and corticosterone plasma levels when compared to NDEP animals, significantly elevated 5-HT1A mRNA levels in the CA1 hippocampal region and, significantly elevated 5-HT2A mRNA levels in the parietal cortex. No changes were observed in 5-HT1A or 5-HT-transporter mRNA levels in the dorsal raphe. Our results indicate that post-synaptic 5-HT receptors in the developing hippocampus and cortex are sensitive to maternal deprivation. Because hippocampal 5-HT1A gene expressions are known to decrease in the adult animal after chronic glucocorticoid elevation, this data also suggests that other mechanisms, perhaps central, predominate during development.

Adrenocorticotropic Hormone↗
PubMed2000

Effects of prenatal dexamethasone on spatial learning and response to stress is influenced by maternal factors.

The present study investigated the effect of prenatal dexamethasone (Dex) exposure on early perinatal events, hippocampal function, and response to stress. Pregnant rats received Dex in the evening water (2.5 microg/ml) or tap water (Veh) from gestational day 15 until delivery. On the day of parturition, pups were randomized, cross-fostered, and reduced to eight or nine per dam. Four groups resulted: Veh-Veh (offspring exposed to Veh in utero, rearing mother treated with Veh during gestation), Veh-Dex, Dex-Veh, and Dex-Dex. Spatial visual memory was evaluated with the Morris water maze. The corticosterone response to restraint stress was examined, and the expression of hippocampal glucocorticoid and mineralocorticoid receptors mRNA was determined by in situ hybridization. Exposure to Dex caused restlessness in mothers, low birth weights, and poor weight gain in the offspring. The Dex-Dex males had impaired spatial learning, inability to rapidly terminate the adrenocortical response to stress, and decreased hippocampal glucocorticoid receptor (GR) mRNA expression. In contrast, Dex-exposed animals reared by Veh-treated mothers had adequate spatial learning, enhanced glucocorticoid feedback, and increased hippocampal GR mRNA. We conclude that the environment provided by a healthy mother during the postnatal period can prevent the detrimental effects of prenatal Dex administration on cognition, GR mRNA expression of the hippocampus, and the quality of the stress response.

Adrenal Cortex↗
PubMed1999

Serotonin 1A receptor messenger RNA regulation in the hippocampus after acute stress.

BACKGROUND: When rats are subjected to chronic stress for 2 weeks, a significant decrease in hippocampal serotonin (5-HT)1A messenger RNA (mRNA) is observed. We wanted to investigate whether stress, administered for shorter periods of time, would result in decreases in 5-HT1A gene expression in hippocampus. METHODS: In one experiment, rats were either stressed daily for 1 week or implanted with two corticosterone pellets to produce elevated corticosterone levels. In another experiment, rats were subjected to a severe acute stressor and sacrificed 1 day or 1 week after the stressor. RESULTS: We found that 24 hours after the acute stress, rats showed a significant decrease in 5-HT1A mRNA levels in CA1 and the dentate gyrus compared to controls. No significant changes in 5-HT1A mRNA levels were detected in any of the other groups. CONCLUSIONS: Although 1 week of chronic stress is not sufficient to cause significant decreases in hippocampal 5-HT1A mRNA levels, a severe and prolonged acute stress is capable of down-regulating, at least transiently, 5-HT1A mRNA gene expression in hippocampus.

Acute Disease↗
PubMed1999

Differential regulation of hippocampal glucocorticoid receptors mRNA and fast feedback: relevance to post-traumatic stress disorder.

Hippocampal glucocorticoid receptors (GR and MR) play an important role in glucocorticoid negative feedback. Abnormalities in negative feedback are found in depression and in post-traumatic stress disorder (PTSD), suggesting that GR and MR might be involved in the pathophysiology of these disorders. Enhanced negative feedback, the PTSD-specific neuroendocrine abnormality, can be induced in animals using a single prolonged stress (SPS) paradigm (a number of different stressors in one prolonged session, 'no stress' interval and a testing session one week later). In the current study, we examined hippocampal GR and MR mRNA distribution in the same animals that exhibited altered negative feedback following the SPS. Seven groups of adult Sprague-Dawley male rats (seven animals each) were used in two studies, comparing unstressed controls to acutely stressed animals (SPS: 24 h group), SPS animals (seven and 14 days), and SPS + chronic stress animals. GR and MR mRNA distribution across hippocampal subfields was studied using in-situ hybridization with 35S-labelled cRNA probes. Acute stress produced down-regulation of GR and MR mRNA across all hippocampal subfields. Seven days later (SPS-7 group), there was a differential recovery, with GR mRNA reaching higher than the prestress levels, and MR mRNA remaining down-regulated. The same differential regulation was present in the 14-day group. Chronically stressed animals that exhibited normal fast feedback also had normalization in their GR and MR mRNA levels. The MR/GR ratio was decreased only in animals that had enhanced fast feedback. These findings suggest that the increase in GR, in hippocampus is involved in the fast feedback hypersensitivity observed in the SPS animals, and might also underlie enhanced dexamethasone sensitivity found in PTSD. Since differential activation of GR and MR can modulate memory, behavioural responsivity, anxiety and fear, change in MR/GR ratio might also explain other PTSD-related phenomena.

Animals↗
PubMed1998

Stress and the developing limbic-hypothalamic-pituitary-adrenal axis.

The postnatal limbic-hypothalamic-pituitary-adrenal (LHPA) axis in the rodent is remarkably different from the adult, both in structure and function. The first 2 weeks postnatally are characterized by a 'silent period' during which the developing animal is hyporesponsive to stress (stress hyporesponsive period-SHRP), followed by a new and unique phase of stress responsiveness when the animal fails to swiftly terminate glucocorticoid secretion. In this review, we summarize our work which focuses on the regulatory biology of the components of the LHPA system and the consequences of its disruption on the adaptive responses of the developing organism. We find that the animal during the first 2 weeks of life responds to an intermittent chronic challenge increasing anterior pituitary POMC post-translational events, while the adult increases genomic events. The result for both the mature and the developing animal is the same, an increase in corticosterone (CS) levels. In addition, we have found evidence of impaired rate sensitive feedback in the weanling animal, as well as changes in ACTH clearance. Similar to the young animal emerging from SHRP, maternally deprived pups during the first week of life exhibit a substantial and sustained ACTH and CS response to stress. In the deprived animal these changes are accompanied by decreases in mineralocorticoid receptor gene expression in the hippocampus, suggesting that changes in mineralocorticoid to glucocorticoid receptor ratios may be important in this phenomena. What has become evident from our studies is that mechanisms underlying normal LHPA development are dynamic, age dependent and distinct to the strategies used by the mature organism to cope with stress.

Adaptation, Psychological↗
PubMed1998

Alpha, beta, and gamma mineralocorticoid receptor messenger ribonucleic acid splice variants: differential expression and rapid regulation in the developing hippocampus.

Two different types of corticoid receptor molecules bind circulating corticosterone in brain: mineralocorticoid receptors (MR) and glucocorticoid receptors. MR exhibit the highest affinity for the endogenous glucocorticoid in the rat, corticosterone. During development, low corticosterone levels influence neurogenesis, and these effects are probably MR mediated. Three MR complementary DNA clones, alpha, beta, and gamma, have been identified in the rodent. All of these MR complementary DNA clones have identical coding regions, but differ significantly at the 5'-untranslated end. Although the functional significance of these three messenger RNA (mRNA) species remains unknown, one hypothesis is that they reflect the ability of the brain to regulate the expression of MR, allowing multiple factors to differentially control transcription in a tissue- and time-specific manner. To investigate this possibility, we examined the presence of these distinct mRNA forms in the developing rat hippocampus (HC). In situ hybridization with specific alpha, beta, and gamma complementary RNA probes was performed in the HC of 3-, 5-, 7-, 12-, 14-, 28-, 35-, and 65-day-old animals. We found that there is differential expression of these forms in each of the HC subfields from infancy to adulthood. y expression appears to be associated with periods of cell birth and increased axonal sprouting. beta expression, on the other hand, may be best linked to periods of synaptogenesis, growth of commissural and associative terminal fields, and possibly active pruning. To explore the possibility that the differential gene expression may be related to corticosterone environment, adrenalectomy was performed. A rapid modulation of the MR mRNA variants (14 h) in an age- and site-specific fashion was seen. These findings suggest that the variation in expression and regulation during development of the multiple MR transcripts could reflect a complex pattern of developmental regulation that may involve a multitude of factors unique to each postnatal age and to the different neuronal populations within the hippocampal formation.

Adrenalectomy↗
PubMed1997

Regulation of 5-HT receptors and the hypothalamic-pituitary-adrenal axis. Implications for the neurobiology of suicide.

Disturbances in the serotonin (5-HT) system is the neurobiological abnormality most consistently associated with suicide. Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is also described in suicide victims. The HPA axis is the classical neuroendocrine system that responds to stress and whose final product, corticosteroids, targets components of the limbic system, particularly the hippocampus. We will review results from animal studies that point to the possibility that many of the 5-HT receptor changes observed in suicide brains may be a result of, or may be worsened by, the HPA overactivity that may be present in some suicide victims. The results of these studies can be summarized as follows: (1) chronic unpredictable stress produces high corticosteroid levels in rats; (2) chronic stress also results in changes in specific 5-HT receptors (increases in cortical 5-HT2A and decreases in hipocampal 5-HT1A and 5-HT1B); (3) chronic antidepressant administration prevents many of the 5-HT receptor changes observed after stress; and (4) chronic antidepressant administration reverses the overactivity of the HPA axis. If indeed 5-HT receptors have a partial role in controlling affective states, then their modulation by corticosteroids provides a potential mechanism by which these hormones may regulate mood. These data may also provide a biological understanding of how stressful events may increase the risk for suicide in vulnerable individuals and may help us elucidate the neurobiological underpinnings of treatment resistance.

Adrenal Cortex Hormones↗
PubMed1997

Lymphocytic hypophysitis presenting with diabetes insipidus in a 14-year-old girl: case report and review of the literature.

UNLABELLED: Lymphocytic hypophysitis is a rare disorder predominantly affecting females during the antepartum or postpartum period. It is characterized by destruction and lymphocytic infiltration of the pituitary gland, probably by an autoimmune process, leading to a pituitary mass lesion and/or various degrees of hypopituitarism. The lesion is usually confined to the adenohypophysis. Posterior pituitary gland or stalk involvement is rare, although patients presenting with diabetes insipidus have been reported. We describe a girl aged 13 years 9 months with lymphocytic hypophysitis who presented with diabetes insipidus and secondary amenorrhea. MRI of the brain revealed a 1 cm enhancing mass in the pituitary stalk. A biopsy of the mass by right pterional craniotomy showed lymphocytic infiltration without neoplastic cells or granuloma formation. To our knowledge, this is the youngest reported patient with a diagnosis of lymphocytic hypophysitis. In this case report, her clinical presentation is discussed along with a review of the literature. CONCLUSION: We present the first childhood case of lymphocytic hypophysitis which is an autoimmune inflammatory disorder of the pituitary gland. Although this is a rare condition in adults, it also needs to be considered in the pediatric population. Conservative management is preferred unless there are signs of increased intracranial pressure. Most importantly, close monitoring for multiple hormone deficiencies is indicated in this condition.

Adolescent↗
PubMed1997

Kinetics of radiolabeled adrenocorticotropin hormone in infant and weanling rats.

Unlike the adult animal, the developing rat has a diminished ability to activate and inhibit the hypothalamic pituitary adrenal axis. In general, a gradual ACTH and corticosterone response to stressors appear after postnatal day 10 and is well established to adult level by weaning age. Although at this age the peak ACTH level is comparable to that of the adult, ACTH levels remain elevated for a longer period of time. The purpose of this study was to investigate the possibility that ACTH metabolism can, in part, explain this prolonged ACTH elevation after a challenge. The plasma half life of disappearance (t1/2, the apparent volume of distribution and metabolic clearance rate (MCR) were determined after injection of a tracer dose of 3-I125-Iodotyrosyl23 ACTH1-39 in rats at 14 and 25 days of age. An adult animal group (65 days old) was used for comparison. The t1/2 for ACTH decreases with age (14 day old = 7.47 +/- 0.9 min; 25 day old = 6.48 +/- 0.4 min; adult = 4.46 +/- 0.2 min) while the volume of distribution remains constant. The MCR is also decreased in the young animals (14 day old = 1.5 +/- 0.19 min; 25 day old = 1.6 +/- 0.18 min; adult = 3.0 +/- 0.56 min). For the first time, it is established that the young animals require longer to clear ACTH from an equivalent volume of blood when compared to the adult. Thus, the kinetic properties of ACTH are different in the developing animal and this partly explains the prolonged ACTH elevation observed after stress challenges.

Adrenocorticotropic Hormone↗
PubMed1996

Regulation of glucocorticoid and mineralocorticoid receptor mRNAs in the hippocampus of the maternally deprived infant rat.

The hypothalamic-pituitary-adrenal (HPA) axis in the developing rat has a limited response to acute challenges between days 3 and 14 of life. Several hypotheses have been proposed to explain this quiescent state. Immaturity of brain, pituitary and adrenal elements or excessive feedback inhibition are common explanations. Recently, a series of studies by Levine and co-workers has shown that prolonged maternal deprivation (24 h) results in increased basal and stress induced corticosterone (CS) levels. An increased adrenal response to ACTH along with an enhanced and sustained ACTH response have been implicated in this phenomenon. A brain structure that appears to be important for normal HPA function is the hippocampus, a structure rich in corticosteroid receptors, which has been hypothesized to play a role in the basal tone of the HPA and in the magnitude and duration of stress responses. Thus, to study further the possible mechanisms leading to an enhanced and sustained ACTH response that is seen in maternally deprived pups, we used in situ hybridization to investigate hippocampal mineralocorticoid (MR) and glucocorticoid receptor (GR) gene expression in 12 groups of animals: six groups involved 24 h maternally deprived (DEP) and non-deprived (NDEP) rat pups at three ages (6-, 9-, and 12-days-old); the other six groups included pups similarly treated, but challenged with an exposure to a mild stressor (saline injection) and sacrificed 1 h thereafter. We found: (1) an age effect for almost every hippocampal subfield for both MR and GR mRNAs: MR increases with age, while GR decreases: (2) down-regulation of MR mRNA in CA1 region in the DEP animals; and (3) down-regulation of GR mRNA, also in CA1, in the saline-injected DEP and NDEP animals. Our results indicate that corticoid receptors in the developing CA1 hippocampal region appear to be sensitive to circulating CS. They also suggest that the relative ratio of GR and MR in the CA1 region may contribute to the enhanced and sustained CS response seen after a mild stressor in deprived animals.

Adrenocorticotropic Hormone↗
PubMed1994

The role of the hippocampal mineralocorticoid and glucocorticoid receptors in the hypothalamo-pituitary-adrenal axis of the aged Fisher rat.

The aging process has been frequently associated with hippocampal neurodegeneration, loss of corticosteroid receptors, and, at the same time, dysfunction of the hypothalamo-pituitary-adrenal (HPA) axis. We were interested in characterizing simultaneously the activity of the HPA axis and status of both corticosteroid receptors (mineralocorticoid or MR and glucocorticoid or GR) in the hippocampus of aged male Fisher-344 rats. We compared intact, adrenalectomized (ADX), and corticosterone-replaced ADX young (5-6 months) and old (26-27 months) rats, examining all the parameters in the same animals. Aged rats exhibited an unaltered basal rhythm and initial corticosterone response to restraint stress. However, the same old animals showed a delayed turn-off of the stress response and did so at different points of the corticosterone circadian cycle. The aged hippocampus showed a 40-50% lower MR and GR binding under all the conditions studied. This aging effect was not attributable to changes in the kinetics, affinity, or nuclear translocation of MR or GR. Intact aged rats exhibited also a 30-40% reduction of hippocampal MR and GR steady-state mRNA levels. Interestingly, after 36 h ADX only the aged hippocampus showed upregulation of MR and GR mRNA content to levels comparable to those in young rats. However, this increase in MR and GR mRNA content was not accompanied by a proportional increase in the Bmax of these receptors, suggesting age-related translational or post-translational alterations. Moreover, corticosterone replacement was able to reverse the ADX-induced increase of MR and GR Bmax in young and old hippocampi but it only reversed the upregulated mRNA levels of MR (and not GR) in the older group. The fact that corticosterone was able to modulate the biosynthetic rate of MR and GR strongly suggests that the decrease of receptors is functional and not simply due to cell death in the aged hippocampus. We propose that in the aged Fisher rat the loss of hippocampal corticosteroid receptors is previous to any change in the circadian rhythm of circulating corticosterone. Furthermore, the altered turn-off of the corticosterone stress response observed in the same animals may be related to the reduction of functional MR and GR but it is not due to high basal levels of corticosterone.

Adrenalectomy↗
PubMed1994

Regulation of hippocampal 5-HT1A receptor gene expression by dexamethasone.

The effect of dexamethasone, a selective GR agonist, on hippocampal, 5-HT1A receptor mRNA expression and 5-HT1A binding was examined using in situ hybridization histochemistry and in vitro receptor autoradiography. One week after adrenalectomy, both 5-HT1A receptor mRNA expression and 5-HT1A binding were increased throughout the hippocampus. Administration of dexamethasone at the time of adrenalectomy significantly attenuated the increases in 5-HT1A mRNA expression in all hippocampal subfields (p < .05, Fisher Test), although 5-HT1A mRNA levels remained significantly higher than sham levels in all subfields with the exception of CA1. However, 5-HT1A binding levels were responsive to dexamethasone administration only within particular hippocampal subfields, CA1, and dentate gyrus. We conclude that GR occupation negatively regulates 5-HT1A receptor mRNA expression within the hippocampus and that 5-HT1A receptor sites are most sensitive to modulation in those hippocampal subfields expressing higher levels of GR receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Pituitary-adrenal response to ether vapor in the weanling animal: characterization of the inhibitory effect of glucocorticoids on adrenocorticotropin secretion.

The hypothalamic-pituitary-adrenal axis is hyporesponsive to stimuli during early life in the rat. Once the adrenocortical response is established, failure to terminate the corticosterone (B) rise is evident after certain stressors, such as ether. The purpose of this study was 2-fold: 1) to investigate the B and ACTH response to ether vapor in young animals and 2) to test the ability of glucocorticoids to inhibit the ether ACTH-stimulated secretion in weanling animals. Rats aged 14, 18, and 25 d and adult rats were subjected to ether vapor for 3 min. Plasma was collected for B and ACTH determination by RIA at 0, 5, 15, 30, 60, and 120; min after ether exposure. Maximum B levels were observed at different times after exposure: 15 min in the adult and 30 min in the younger animals. In addition, B levels were significantly elevated at 60 min in the d 25 and d 18 rats compared with the adult (d 25 = 672.4 +/- 28.9, d 18 = 744.6 +/- 31.7, adult = 323.2 +/- 8.7 mol/L +/- SEM; d 25 = 23.3 +/- 1.0, d 18 = 25.8 +/- 1.1, adult = 11.2 +/- 0.3 micrograms/dL +/- SEM). The B delay observed in the younger animals was not due to a delayed ACTH response because maximal ACTH values were observed 5 min after ether exposure in all ages (d 14 = 21.9 +/- 4.8, d 18 = 35.8 +/- 21.3, d 25 = 82.01 +/- 16.5, adult = 98.9 +/- 25.2 x 10(-12) mol/L +/- SEM). However, in the d 25 rats the ACTH level remained significantly elevated 30 min after the ether vapor challenge (5 min = 86.9 +/- 25.2, 30 min = 61.8 +/- 4.8, 60 min = 15.3 +/- 4.1 x 10(-12) mol/L +/- SEM). The delay to return to resting ACTH levels was consistent with the time delay observed for the B release from the adrenal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

Development of pituitary pro-opiomelanocortin gene and peptide expression: characterization and effect of repeated intermittent maternal isolation.

The dynamics of pro-opiomelanocortin (POMC) biosynthesis in the adult rat are altered by demands imposed on the system, such that acute stress increases in the efficiency of anterior pituitary (AP) posttranslational events, while repeated stress increases pretranslational events. In contrast, the developing animal has a limited adrenocortical response to acute stress during the first 2 weeks of life (stress nonresponsive period). In this study, we investigated how the maturing AP and intermediate lobe (IL) POMC cells respond to repeated demand. Measurements of AP and IL POMC mRNA and POMC peptides were performed using Northern gels and radioimmunoassay, respectively. Plasma ACTH and corticosterone measurements were also performed. Maternal isolation, for 1 h on 3 consecutive days, was used as a repeated stress stimulus. The developing AP and IL exhibit an age-related increase in POMC mRNA and peptide levels. On the other hand, AP and IL do not respond to repeated intermittent maternal isolation during the first 2 weeks of life. However, a significant corticosterone release is seen in the 14 and 21-day-old animals. A change in POMC mRNA level is only detected in the 21-day-old AP where levels decrease. Therefore, an adrenocortical response to repeated intermittent maternal isolation predates the appearance of glucocorticoid inhibition of POMC expression in the 21-day-old animal. We propose that an immature neuronal inhibitory circuit during the 3rd week of life causes a sustained corticosteroid response which may in turn trigger AP-delayed feedback.

Animals↗